An epidemiological study has concluded that high consumption of fruits and vegetables, rich specifically in two dietary carotenoids, lutein and zeaxanthin, reduces the risk of a degenerative eye disease called Age-related Macular Degeneration (AMD). High intake of carotenoid-rich fruits and vegetables results in the absorption of 25 dietary carotenoids which are converted to 9 metabolites in humans. Although all 34 carotenoids have been identified in human serum, milk, and tissues at varying concentrations, the major carotenoids found in the human retina, lens, and iris are lutein and zeaxanthin. In addition, two of the major oxidation products of lutein and zeaxanthin, 3'-oxolutein and 3'-epilutein, have also been shown to be present in retina and other ocular tissues at relatively low concentrations. One of the underlying hypothesis for the protective role of lutein and zeaxanthin has been based on the ability of these carotenoids to act as antioxidant and protect the human macula from photo-oxidation. The overall objective of his three-year proposal is to investigate the bioavailability, oxidative metabolism, retinal pigment density, and possible toxicity in primates supplemented with chronic and pharmaceutical doses of lutein, zeaxanthin, and their 1/1 combination. These studies will also evaluate possible interaction between lutein, zeaxanthin, and fat soluble vitamins such as vitamins A and E. In year one, chronic daily intake of lutein and zeaxanthin at a high dose of up to three hundred fold of the dietary levels, will be examined to establish safety or possible toxicity. In year two, 18 primates will be daily supplemented with lutein, zeaxanthin, and their 1/1 combination at a pharmaceutical dose of 0.5 mg/Kg/body weight to establish the optimum macular pigment density and correlate these values to plasma concentration of these carotenoids. In year three, 3 primates will be daily dosed with isotopically labeled zeaxanthin for a duration of six months. The study with labeled zeaxanthin allows the investigators to determine the possible metabolic conversion of this carotenoid to its oxidation products (metabolites) in serum and ocular tissues. The results from these studies will enable researchers to safely design and conduct clinical trials to investigate the efficacy of lutein and zeaxanthin supplementation in the prevention and treatment of AMD and cataract. Lutein/zeaxanthin supplements have widely used as a nutritional supplement un the U.S. since 1995, while safety and efficacy of these carotenoids has not yet been established.